scholarly journals Plasma CircRNAs for First Trimester Prediction of Preeclampsia and Potential Biomarkers

2021 ◽  
Vol 21 (03) ◽  
Author(s):  
Jie Lu
Keyword(s):  
Rna Sequencing ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
First Trimester ◽  
Receiver Operator Characteristic Curve ◽  
Curve Analysis ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Qrt Pcr

ABSTRACT This study investigated expression profiles and mechanisms of circular RNAs on preeclampsia patients between 7-14 weeks. RNA sequencing demonstrated 12,579 circRNAs (7,684 upregulated and 4,895 downregulated) expressed differentially in 8 pairs of plasma samples from preeclampsia patients and healthy controls. Predicted 15 upregulated and 9 downregulated circRNAs then were assessed through qRT-PCR in 50 preeclampsia patients and 30 controls. Differentially expressed circRNAs in preeclampsia patients and controls were analyzed by RNA sequencing and gene ontology, Kyoto Encyclopedia of Genes and Genomes and circRNA-miRNA-mRNA network analyzed data. Hsa_circ_0046677 and hsa_circ_0029703 were markedly increased in preeclampsia patients. Receiver operator characteristic curve analysis indicated the area under the curve was 0.083 for hsa_circ_0046677 and 0.965 for hsa_circ_00429703 while the sensitivity and specificity of these two genes were 78 percent, 88 percent and 83 percent, 93 percent, respectively. Hsa_circ_0046677 and hsa_circ_00429703 had enormous potentials for diagnosing preeclampsia of pregnant women in the first trimester.

scholarly journals Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary Cholangitis Patients

2017 ◽  
Vol 44 (4) ◽  
pp. 1271-1281 ◽  
Author(s):  
Jiajia Zheng ◽  
Zhenrong Li ◽  
Tiancheng Wang ◽  
Yang Zhao ◽  
Yongfeng Wang
Keyword(s):  
Expression Profile ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Group Versus ◽  
Target Prediction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Primary Biliary Cholangitis ◽  
Healthy Controls ◽  
Qrt Pcr

Background/Aims: Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases, including autoimmune diseases. However, their role in primary biliary cholangitis (PBC) remains unclear. Here, we aimed to determine the circRNA expression profile in plasma from PBC patients and further explore the value of circRNA in diagnosing PBC. Methods: CircRNA microarrays were used to determine circRNA expression profiles in plasma samples from 6 PBC patients and 6 healthy controls. Statistical analyses identified differentially expressed circRNAs, and these circRNAs were verified by qRT-PCR in 29 PBC patients and 30 healthy controls. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. Results: Our results indicated that there were 18 up-regulated and 4 down-regulated circular RNAs in the plasma from PBC patients compared with that from healthy individuals. Among the differentially expressed circRNAs, hsa_circ_402458 (P=0.0033), hsa_circ_087631 and hsa_circ_406329 (P=0.0185) were up-regulated, and hsa_circ_407176 (P=0.0066) and hsa_circ_082319 were down-regulated in the PBC group versus the healthy group as demonstrated by qRT-PCR. In particular, hsa_circ_402458 was significantly higher in PBC patients not receiving UDCA treatment than in PBC patients receiving UDCA treatment (P=0.0338). The area under the receiver operating characteristic curve for hsa_circ_402458 for diagnosing PBC was 0.710 (P=0.005). For hsa_circ_402458, two putative miRNA targets, hsa-miR-522-3p and hsa-miR-943, were predicted. Conclusions: circRNA dysregulation may play a role in PBC pathogenesis, and hsa_circ_402458 shows promise as a candidate biomarker for PBC.

scholarly journals Serum N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker of Critical Pulmonary Stenosis in Neonates

2022 ◽  
Vol 9 ◽  
Author(s):  
Zhiwei Lin ◽  
Yanru Chen ◽  
Lin Zhou ◽  
Sun Chen ◽  
Hongping Xia
Keyword(s):  
Natriuretic Peptide ◽  
Characteristic Curve ◽  
Pulmonary Stenosis ◽  
Area Under The Curve ◽  
Rank Correlation ◽  
Length Of Hospital Stay ◽  
Receiver Operator Characteristic Curve ◽  
Curve Analysis ◽  
Positive Correlation ◽  
Critical Pulmonary Stenosis

Objectives: To determine the efficacy of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in predicting critical pulmonary stenosis (CPS) in neonates.Methods: All neonates with pulmonary stenosis (PS) admitted to the neonatal intensive care unit of Xinhua Hospital from October 2014 to December 2020 were retrospectively reviewed. Infants with serum NT-proBNP levels measured within 48 h after birth were enrolled and divided into CPS and non-CPS groups. Serum NT-proBNP levels and cardiac Doppler indices were compared between the two groups. Correlations were determined using the Spearman's rank correlation coefficient. Receiver operator characteristic curve analysis was used to explore the predictive value of NT-proBNP for identifying neonatal CPS.Results: Among 96 infants diagnosed with PS by echocardiography, 46 were enrolled (21 and 25 in the non-CPS and CPS groups, respectively). Serum NT-proBNP levels were significantly higher in the CPS group than in the non-CPS group [3,600 (2,040–8,251) vs. 1,280 (953–2,386) pg/ml, P = 0.003]. Spearman's analysis suggested a positive correlation between Ln(NT-proBNP) levels and the transvalvular pulmonary gradient (r = 0.311, P = 0.038), as well as between Ln(NT-proBNP) levels and pulmonary artery velocity (r = 0.308, P = 0.040). Receiver operating characteristic curve analysis showed that a cutoff serum NT-proBNP level of 2,395 pg/ml yielded a 66.7 and 78.9% sensitivity and specificity for identifying CPS, respectively. The area under the curve was 0.784 (95% CI, 0.637–0.931). A positive correlation was found between Ln(NT-proBNP) and length of hospital stay (r = 0.312, P < 0.05).Conclusion: Serum NT-proBNP level was positively correlated with PS severity and could be used as a biomarker to identify CPS in neonates.

scholarly journals Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1247
Author(s):  
Anne Worthington ◽  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Luca Donofrio ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Initial Response ◽  
Healthy Controls ◽  
Painful Diabetic Neuropathy ◽  
Stimulus Response ◽  
Rate Dependent ◽  
Potential Biomarker ◽  
Spinal Inhibition

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2–4 and 2–5 at 1 Hz, AUC = 0.84 (95%CI 0.76–0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

scholarly journals Serum Extracellular Vesicle-Derived circHIPK3 and circSMARCA5 Are Two Novel Diagnostic Biomarkers for Glioblastoma Multiforme

2021 ◽  
Vol 14 (7) ◽  
pp. 618
Author(s):  
Michele Stella ◽  
Luca Falzone ◽  
Angela Caponnetto ◽  
Giuseppe Gattuso ◽  
Cristina Barbagallo ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Roc Analysis ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Size Exclusion ◽  
Circular Rnas ◽  
Diagnostic Biomarkers ◽  
Exclusion Chromatography

Glioblastoma multiforme (GBM) is the most frequent and deadly human brain cancer. Early diagnosis through non-invasive biomarkers may render GBM more easily treatable, improving the prognosis of this currently incurable disease. We suggest the use of serum extracellular vesicle (sEV)-derived circular RNAs (circRNAs) as highly stable minimally invasive diagnostic biomarkers for GBM diagnosis. EVs were isolated by size exclusion chromatography from sera of 23 GBM and 5 grade 3 glioma (GIII) patients, and 10 unaffected controls (UC). The expression of two candidate circRNAs (circSMARCA5 and circHIPK3) was assayed by droplet digital PCR. CircSMARCA5 and circHIPK3 were significantly less abundant in sEVs from GBM patients with respect to UC (fold-change (FC) of −2.15 and −1.92, respectively) and GIII (FC of −1.75 and −1.4, respectively). Receiver operating characteristic curve (ROC) analysis, based on the expression of sEV-derived circSMARCA5 and circHIPK3, allowed us to distinguish GBM from UC (area under the curve (AUC) 0.823 (0.667–0.979) and 0.855 (0.704 to 1.000), with a 95% confidence interval (CI), respectively). Multivariable ROC analysis, performed by combining the expression of sEV-derived circSMARCA5 and circHIPK3 with preoperative neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR) and lymphocyte to monocyte (LMR) ratios, three known diagnostic and prognostic GBM markers, allowed an improvement in the GBM diagnostic accuracy (AUC 0.901 (0.7912 to 1.000), 95% CI). Our data suggest sEV-derived circSMARCA5 and circHIPK3 as good diagnostic biomarkers for GBM, especially when associated with preoperative NLR, PLR and LMR.

scholarly journals COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1018
Author(s):  
Abby C. Lee ◽  
Grant Castaneda ◽  
Wei Tse Li ◽  
Chengyu Chen ◽  
Neil Shende ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Expression Profiles ◽  
Immune Dysregulation ◽  
Left Ventricular ◽  
Recurrent Event ◽  
Healthy Controls ◽  
Sequencing Data ◽  
Peripheral Blood Mononuclear

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.

scholarly journals Adrenomedullin Is a Diagnostic and Prognostic Biomarker for Acute Intracerebral Hemorrhage

2021 ◽  
Vol 43 (1) ◽  
pp. 324-334
Author(s):  
Francisco J. Julián-Villaverde ◽  
Laura Ochoa-Callejero ◽  
Eva Siles ◽  
Esther Martínez-Lara ◽  
Alfredo Martínez
Keyword(s):  
Hemorrhagic Stroke ◽  
Prognostic Biomarker ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Nitroso Compounds ◽  
Healthy Controls ◽  
Stroke Patients ◽  
Important Health ◽  
Acute Intracerebral Hemorrhage ◽  
Changes Over Time

Hemorrhagic stroke remains an important health challenge. Adrenomedullin (AM) is a vasoactive peptide with an important role in cardiovascular diseases, including stroke. Serum AM and nitrate–nitrite and S-nitroso compounds (NOx) levels were measured and compared between healthy volunteers (n = 50) and acute hemorrhagic stroke patients (n = 64). Blood samples were taken at admission (d0), 24 h later (d1), and after 7 days or at the time of hospital discharge (d7). Neurological severity (NIHSS) and functional prognosis (mRankin) were measured as clinical outcomes. AM levels were higher in stroke patients at all times when compared with healthy controls (p < 0.0001). A receiving operating characteristic curve analysis identified that AM levels at admission > 69.0 pg/mL had a great value as a diagnostic biomarker (area under the curve = 0.89, sensitivity = 80.0%, specificity = 100%). Furthermore, patients with a favorable outcome (NIHSS ≤ 3; mRankin ≤ 2) experienced an increase in AM levels from d0 to d1, and a decrease from d1 to d7, whereas patients with unfavorable outcome had no significant changes over time. NOx levels were lower in patients at d0 (p = 0.04) and d1 (p < 0.001) than in healthy controls. In conclusion, AM levels may constitute a new diagnostic and prognostic biomarker for this disease, and identify AM as a positive mediator for hemorrhagic stroke resolution.

scholarly journals A novel combination of serum microRNAs for the detection of early gastric cancer

2021 ◽  
Author(s):  
Seiichiro Abe ◽  
Juntaro Matsuzaki ◽  
Kazuki Sudo ◽  
Ichiro Oda ◽  
Hitoshi Katai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Cancer Center ◽  
Serum Samples ◽  
Retrospective Case ◽  
Serum Mirnas ◽  
Validation Set

Abstract Background The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene®) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.

scholarly journals Identification of LOC338963 and AP3B2 as Potential Biomarkers for Lambert-Eaton Myasthenic Syndrome

2021 ◽  
Author(s):  
Fei Yang ◽  
Feng Jing ◽  
Yang Li ◽  
Shanshan Kong ◽  
Shimin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Myasthenic Syndrome

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder associated with muscle weakness and small-cell lung cancer. Here, we used microarray analysis to identify long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) that might serve as biomarkers for LEMS.Methods: Plasma lncRNA and mRNA expression profiles of three patients with paraneoplastic LEMS and three healthy controls were analyzed using Arraystar Human lncRNA Microarray v4.0. Differentially expressed lncRNAs and adjacent mRNAs were analyzed jointly, and candidates were verified in individual samples by quantitative real-time polymerase chain reaction (qRT-PCR). The identified lncRNAs and mRNAs were evaluated in nine patients with paraneoplastic LEMS, eight patients with non-tumor LEMS, and four patients with small cell lung cancer (SCLC). Results: A total of 320 lncRNAs were differentially expressed in patients with paraneoplastic LEMS compared to healthy controls (fold change >1.5, P < 0.05), and nine were further evaluated. One of the identified lncRNAS, LOC338963 (NR_031439), is known to regulated the expression of the mRNA AP3B2, and both were upregulated more than 2-fold in patients with paraneoplastic LEMS compared to healthy controls. Furthermore, qRT-PCR analysis revealed significant upregulation of LOC338963 (NR_031439) and AP3B2 expression in patients with paraneoplastic LEMS compared to those with either non-tumor LEMS (2.37- and 5.06-fold, respectively) or SCLC (4.36- and 14.97-fold, respectively).Conclusions: Plasma LOC338963 (NR_031439) and AP3B2 were found to be upregulated in LEMS and might be used as diagnostic biomarkers for this disease.

Identification of Circulating hsa_circ_0063425 and hsa_circ_0056891 as Novel Biomarkers for Detection of Type 2 Diabetes

2021 ◽  
Author(s):  
Ya-Ke Lu ◽  
Xi Chu ◽  
Shuo Wang ◽  
Yue Sun ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Early Detection ◽  
Expression Profiles ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Mirna Targets ◽  
Novel Biomarkers

Abstract Context Circular RNAs (circRNAs), which are involved in the development of diseases by regulating gene expression, have become promising novel biomarkers for diseases. Objective The aim of the present study was to identify the circulating circRNA biomarkers for early detection of type 2 diabetes (T2D). Methods The circRNA expression profiles were screened by microarray and compared between 5 new T2D cases and 5 healthy controls. The expression of candidate circRNAs that may be involved in the insulin phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway were validated by RT-qPCR in a second sample with 30 T2D cases and 30 controls. The association between circRNAs and T2D and their clinical significances were further assessed by logistic regression model, correlation analysis, and ROC curve in a large cohort comprising 313 subjects. The microRNA (miRNA) targets of circRNAs were verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, impaired fasting glucose (IFG), and insulin resistance. The 2-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls, especially when body mass index was integrated. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significant positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels. Conclusion Downregulated hsa_circ_0063425 and hsa_circ_0056891 might contribute to the pathogenesis of T2D. They are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling.

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